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 Table of Contents  
Year : 2019  |  Volume : 8  |  Issue : 14  |  Page : 109-114

Stress response associated with elective cesarean delivery: A comparison of the effect of general versus subarachnoid anesthesia

1 Department of Anaesthesia, University of Abuja Teaching Hospital, University of Abuja, Gwagwalada, FCT, Abuja, Nigeria
2 Department of Anaesthesia, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
3 Department of Obstetrics and Gynaecology, University of Abuja Teaching Hospital, University of Abuja, Gwagwalada, FCT, Abuja, Nigeria

Date of Submission01-Oct-2018
Date of Acceptance01-Aug-2019
Date of Web Publication04-Oct-2019

Correspondence Address:
Dr. Olumide Adeleke Akitoye
Department of Anaesthesia, University of Abuja Teaching Hospital, Gwagwalada, FCT, Abuja
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/nnjcr.nnjcr_37_18

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Context: Pregnancy, surgery, and anesthesia are identified forms of stress to the body. Sustained response to stress has been associated with increased morbidity and mortality. Aim: The aim of the study is to determine the effect of anesthetic techniques on the response to the stress of surgery and anesthesia. Study Design: This was a prospective, randomized, double-blind study. Subjects and Methods: One hundred and forty patients scheduled for elective cesarean section were recruited and randomized into two groups: general anesthesia and subarachnoid anesthesia. Heart rate (HR), blood glucose, and cortisol levels were used to evaluate the body response to stress. Blood samples to estimate glucose and cortisol levels were taken the night of the day before surgery, just before induction, 30 min after induction, 60 min after induction, and 24-h postsurgery. The Statistical Package for the Social Sciences Version 23 was used for analysis to find the mean and standard deviation of both categorical and noncategorical variables. The Independent t-test and two-tailed test were used to show the differences in the HR, blood glucose, and cortisol levels within and between the general anesthesia and subarachnoid anesthesia groups. Results: The two groups were comparable in terms of age, height, weight, and American Society of Anesthesiologists status. The changes in HR and blood glucose were similar in both groups. However, a statistically significant difference was noted in the level of cortisol between the two groups at 60-min postskin incision with 494 ± 161 nmol/L in the general anesthesia group as opposed to 347 ± 161 nmol/L in the subarachnoid anesthesia group with a P = 0.01. Conclusions: The study demonstrated that subarachnoid anesthesia offers an advantage over general anesthesia in terms of the reduction to stress response to surgery and anesthesia. However, patient's choice and the urgency in the delivery of the fetus should be considered in choosing a mode of anesthesia.

Keywords: Anesthesia, cesarean, response, stress

How to cite this article:
Akitoye OA, Atiku M, Adewole ND. Stress response associated with elective cesarean delivery: A comparison of the effect of general versus subarachnoid anesthesia. N Niger J Clin Res 2019;8:109-14

How to cite this URL:
Akitoye OA, Atiku M, Adewole ND. Stress response associated with elective cesarean delivery: A comparison of the effect of general versus subarachnoid anesthesia. N Niger J Clin Res [serial online] 2019 [cited 2020 Apr 4];8:109-14. Available from: http://www.mdcan-uath.org/text.asp?2019/8/14/109/268534

  Introduction Top

Stress, a physical or perceived threat to homeostasis, arises as a result of the introduction of agents referred to as stressors.[1] Stress response manifests with autonomic, hormonal, and metabolic changes.[2] The catecholamine (epinephrine and norepinephrine) and the glucocorticoids are the two categories of hormones that form the central components of the endocrine response. Surgery is a known stressor to the body.[2] Prolonged surgical stress stimulates biochemical reactions throughout the body, which lead to delayed postoperative recovery and increased morbidity and mortality.[3] Sufficient suppression of the pain pathways (antinociception) reduces stress responses during surgery.[3]

Pregnancy is a form of stress, as it requires both physiological and biochemical adaptations in the body of a woman.[4] Surgery may further increase the stress already experienced by the pregnant woman.

Glucose and cortisol are metabolic substrates that have been shown to correlate well with body response to stress.[5] This study aims at quantifying the change in the blood level of these substrates during the perioperative period, as a measure of the stress experienced by the parturient during cesarean section.

  Subjects and Methods Top

This is a prospective, randomized, double-blind study. After approval by the Ethics Committee, 140 patients undergoing elective cesarean section were recruited. Written informed consent was obtained from all patients. Inclusion criteria were American Society of Anesthesiologists (ASA) I and II patients scheduled for elective cesarean section. Exclusion criteria were ASA III or greater, patients on medication known to affect metabolism, e.g., corticosteroids, β-adrenergic blockers, inadequate subarachnoid block requiring parenteral analgesia, or conversion to general anesthesia after subarachnoid block. Also excluded were some conditions relating to contraindication for spinal anesthesia, e.g., history of severe sciatica or back surgery, coagulopathy, infection around the lumbar puncture site, aortic stenosis, or spinal deformity.

Patients were assigned to receive either general anesthesia (Group A, n = 70) or subarachnoid block (Group B, n = 70) using the table of random numbers.

All patients included in the study were reviewed preoperatively the day before surgery and fasted for at least six 6 h for solid food and 2 h for clear fluids. Premedication (tablet ranitidine 150 mg) was administered to all patients at 6 pm the night before surgery and 1–2 h before surgery. The height and weight of the patients' were measured preoperatively. Patients were transported to the operating theater with a left lateral tilt using a wedge under the right hip. The tilt was maintained on the operation table up to delivery of the baby to avoid aortocaval compression. Intravenous access was established using a size 16G intravenous cannula and hemodynamic monitoring (noninvasive arterial blood pressure, electrocardiogram, and pulse oximetry) commenced before induction of anesthesia and continued until discharge from the recovery room. Intravenous fluid was administered to all patients at a rate of 8–10 ml/kg/h preinduction and 1.5–3 ml/kg/h during surgery. Significant blood loss was replaced with compatible blood.

In the patients randomized to receive general anesthesia (Group A), induction of general anesthesia was administered with 4 mg/kg of sodium thiopentone and suxamethonium (1.5 mg/kg) was administered for tracheal intubation, with an appropriate size endotracheal tube. Anesthesia was maintained with isoflurane (0.75 MAC value) in oxygen and atracurium 0.3–0.5 mg/kg. Following the delivery of the baby, oxytocin 10 units bolus was given followed by an infusion of 10 units in 500 ml of 0.9% saline, and morphine 0.15 mg/kg was administered intravenously for analgesia. At the end of the surgery, isoflurane was turned off and residual neuromuscular block reversed with neostigmine 2.5 mg, and atropine 1.2 mg. Patients were extubated awake in the left lateral position with a slight head-down tilt.

In the patients randomized to receive subarachnoid block (Group B), coloading was done with 10 ml/kg of 0.9% saline. Lumbar puncture was performed as an aseptic procedure using a 25G pencil-point spinal needle with the patient in the sitting position and legs on a stool with the knees higher than the hip and 0.5% heavy bupivacaine (2.0–2.5 ml) injected into the subarachnoid space. After injection of the local anesthetic agent, patients were made to lie supine with left-lateral displacement of the uterus to achieve a sensory block level up to T5/6 as confirmed by loss of sensation to cold stimulus. Supplemental oxygen (4 l/min) was administered by face mask to all the patients.

In both groups, postoperative pain relief in the first 24 h was achieved with morphine 10 mg IM 4 hourly as required to achieve pain score of <4 on a Visual Analog Scale (0–10). Surgery time was considered as the interval between skin incision and the time of the last stitch. Heart rates (HRs) of patients in both groups were recorded at preoperative review by 6 pm the night before surgery, before induction, 30-min postskin incision, 60-min postskin incision, at recovery room, and 24-h postoperatively.

Venous blood samples for glucose measurement were drawn a day before surgery (6 pm the night before), before the induction of anesthesia, at 30 min, 60 min after induction, and 24 h after surgery, while that for cortisol levels were taken a day before surgery (6 pm the night before), 60-min postskin incision, and 24-h postsurgery. Blood samples for glucose were assayed immediately using the portable Accu-Chek glucometer (Roche Diagnostics, Mannheim, Germany) which had been previously standardized with results from the main hospital laboratory. Samples for serum cortisol levels were collected and analyzed by means of an immunofluorescence technique using the TDx/FLx Autoanalyser manufactured by Abbott Laboratories, Diagnostics Division. Abbott Park, IL 60064, USA.

  Results Top

Upon approval of the hospital's ethics committee, 140 patients were enrolled in the study after obtaining informed written consent. No patient was excluded from the study based on exclusion criteria. Five patients were excluded from the study in Group B: two patients were excluded from the study because of inadequate block height while the other three patients opted for general anesthesia, while in the theater, leaving a total of 65 patients in Group B [Figure 1].
Figure 1: Consort flow diagram

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Both groups were comparable with regard to age, height, weight, and ASA classification [Table 1]. The mean age of patients in Group A was 27 ± 3 years, while that in Group B was 26 ± 3 years. The mean height and weight for both groups were 162 cm ± 7 and 68 kg ± 3, respectively.
Table 1: Demographic data

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Group B patients had a shorter duration of surgery (48 min ± 7) and a reduced blood loss (428 ± 73 mls) when compared with the patients in Group A [Table 2], but these were not statistically significant (P< 0.05).
Table 2: Surgical data

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The perioperative HR increased gradually from the basal value at 6 pm on the day before surgery until 60-min postskin incision in both groups though with a higher increase in the general anesthesia group (P = 0.90). The HR, however, reduced from the recovery period and was almost at baseline value by 24-h postoperatively (P = 0.79) [Figure 2].
Figure 2: Perioperative changes in heart rate. PSI = Postskin incision

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Similarly, changes in the perioperative plasma glucose concentrations were similar in both groups. The blood glucose concentration reduced from the level at the preoperative review to before induction in the theater in both groups (P = 0.45). Thereafter, an increased was noted up to 60-min postskin incision in both groups though higher in the general anesthesia group (P = 0.49) with a decline toward the preoperative value from the recovery period to 24-h postoperatively (P = 0.46) [Figure 3].
Figure 3: Perioperative blood glucose concentration. Preop - At preoperative review, PSI - Postskin incision

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Plasma cortisol concentrations showed a marked increase at 60-min postskin incision in both groups when compared to the value at preoperative review. Thereafter, a reduction was noted in the general anesthesia group at 24-h postoperatively, while the subarachnoid group showed a slight increase in value. The increase in the value of cortisol in the general anesthesia group from preoperative review to 60-min postskin incision was found to be statistically significant (P< 0.05). Likewise, the difference in the value of serum cortisol in both groups at 60-min postskin incision was also statistically significant (P< 0.05) [Figure 4] and [Table 3].
Figure 4: Perioperative plasma concentrations of cortisol

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Table 3: Perioperative plasma concentrations of cortisol (mean±standard deviation)

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  Discussion Top

The stress response was previously thought to be an adaptive homeostatic response to a physiological insult, enhancing resistance to stress.[6] However, there is growing evidence that the stress response is actually detrimental and is associated with postoperative morbidity. It has adverse effects on several key physiological systems, including cardiovascular, respiratory, and gastroenterological systems.[6] Following trauma from accident or surgery, a characteristic two-phase neuroendocrine response (an initial “ebb” or shock phase followed by a “flow” or hyperdynamic phase) in proportion to the extent of injury is elicited. In surgery, the flow phase is the stress response.[2]

The mean fasting plasma glucose level in Nigerian pregnant women in the third trimester was reported as 3.8 ± 0.85 mmol/L.[7] Blood glucose concentration rises as soon as surgery begins. Cortisol and catecholamines promote glucose production as a result of increased hepatic glycogenolysis and gluconeogenesis.[2]

Excessive intraoperative stress may influence the outcome, increase length of hospital stay, and overall cost of hospital care.[8],[9] Additional stress to parturient that could be present due to factors such as emergency surgeries, stress response to the pain of labor, and varying duration of preoperative fasting was avoided by studying elective cases. Although the surgeries were performed by different surgeons, they were in the senior registrar and consultant cadre.

This study demonstrates similar changes in the blood glucose levels in the perioperative period in both groups but showed a significant difference in the cortisol levels as parturient who had subarachnoid anesthesia had lower levels of cortisol than those who had general anesthesia. It is, therefore, apparent that subarachnoid anesthesia is more effective in the reduction of stress arising from surgery and anesthesia.

The patients were studied in terms of the changes in HR, volume of crystalloid used during the surgery, and the duration of surgery. In general, the stress response to any injury is proportional to the severity and the duration of application of the insult.[2] HR and the mean arterial pressure have been used as measures of the global hemodynamics of patients.[10],[11] Our study showed that the HR increased from the basal value at 6 pm on the day before surgery to reach its peak at 60-min postskin incision in both groups with a higher value in the general anesthesia group. This is in keeping with the fact that adequate subarachnoid block was achieved before skin incision in Group B compared to Group A, where the analgesic (morphine) was commenced after the delivery of the baby. This supports the findings of Loughran et al.[12] and Roizen et al.[13] They found that increasing doses of halothane and morphine were associated with reduced cardiovascular response to incision and that adequate level of spinal anesthesia gives no cardiovascular response to skin incision. This is probably because general anesthesia for cesarean section involves rapid induction with intubation and maintenance under light plane of anesthesia. Pflug and Halter[14] established that the stress of intra-abdominal surgery is not blocked by clinical anesthetic levels of inhalational agents, e.g., halothane and isoflurane.

Duration of surgery was used as an indication of the duration of application of the stressing incident. Patients in Group B had a slightly shorter duration of surgery when compared to those in Group A, but this was not statistically significant. The reason could not be ascertained as the surgeons were blinded to the study objectives. Previous studies did not show any statistically significant difference in the duration of surgery with these techniques.[15],[16]

In our study, the plasma glucose and cortisol concentrations in both groups were comparable at preoperative review [Figure 3] and [Figure 4]. The plasma glucose concentrations in both groups, however, showed a decline from the preoperative value to that measured at induction. We attributed this to the preoperative fasting of patients, as no antistress agent was used except for psychological support and counseling given to patients at the preoperative review. This observation could be the reason for the changes and development in preoperative fasting guidelines in recent times.[17] Emphasis is on the reduction of the period of preoperative fasting with the encouragement and introduction of clear fluid within 2 h of surgery.[18]

Intraoperatively, the plasma glucose concentrations in both groups increased in a similar fashion with marked increase at 60-min postskin incision and with slightly higher value in Group A [Figure 3]. This period most likely correlates with the point of maximum response to the stress of surgery and anesthesia. A comparison of the changes in the plasma glucose levels from the day before surgery to 60-min postskin incision in both groups showed that the stress response to surgery is more than that of the induction of anesthesia or to the emotional stress of being brought to the theater. This finding agrees with that of Allison et al.[19] who stated that the stress of surgery seems to be more important than that of anesthesia in causing a rise in blood sugar level. Our study showed a little rise in the blood glucose level at 30-min postskin incision when compared to the value at induction. Thereafter, there was a marked difference between the blood glucose level at 60-min postskin incision and the value at 30-min postskin incision in both groups. The difference in the blood glucose level between the two groups was abolished within the first 24 h of surgery. Our findings correlate well with the findings of Møller et al.[20] who demonstrated a similar increase in the blood glucose level in the two groups but with statistical significance. However, Amiri et al.[21] in a study comparing surgical stress responses during spinal and general anesthesia in curettage surgery for therapeutic abortion showed no statistical difference in blood glucose at 10 min before and 20 and 60 min after initiation of anesthesia.

Serum cortisol levels are correlated with the intensity, duration, and type of stress that caused them.[22] Various kinds of stress cause an increase in the secretion of adrenocorticotrophic hormone from the adenohypophysis, and (within a few minutes) an increase in secretion of cortisol from the adrenal cortex. This increase returns to normal in due course of time.[23],[24] Preoperatively, the plasma cortisol concentration was comparable in both groups. However, measurement of cortisol concentration at 60-min postskin incision revealed a significant rise from the baseline value in both groups. Furthermore, this study revealed a significantly higher cortisol concentration at 60-min postskin incision in Group A when compared to the concentration in Group B at this same time (P< 0.05). Kale et al.[25] in their study on the effect of general and spinal anesthesia on maternal and newborn cortisol levels in elective deliveries found lower maternal and newborn cortisol levels with spinal anesthesia compared to general anesthesia and concluded that spinal anesthesia could be a more preferable technique in elective cesarean section due to reduced stress response observed with this technique. Milosavljevic et al.[22] also demonstrated a statistically significant difference in the level of cortisol in both groups. It was, however, observed in our study that the serum level of cortisol at 24-h postsurgery was slightly more than the value at 60-min postskin incision in the subarachnoid group. In contrast, the general anesthesia group showed a decline at 24-h postsurgery.

  Conclusions Top

This study has demonstrated that regional anesthesia offers an advantage over general anesthesia in terms of the reduction to stress response to surgery and anesthesia. Hence, regional anesthesia should be preferred as the technique of choice for cesarean section coupled with its proven advantages (lesser incidence of pulmonary aspiration of gastric contents, early mobilization, etc.). However, patient's choice and the urgency in the delivery of the fetus should be taken into consideration.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Loughran PG, Moore J, Dundee JW. Maternal stress response associated with caesarean delivery under general and epidural anaesthesia. Br J Obstet Gynaecol 1986;93:943-9.  Back to cited text no. 12
Roizen MF, Horrigan RW, Frazer BM. Anesthetic doses blocking adrenergic (stress) and cardiovascular responses to incision – MAC BAR. Anesthesiology 1981;54:390-8.  Back to cited text no. 13
Pflug AE, Halter JB. Effect of spinal anesthesia on adrenergic tone and the neuroendocrine responses to surgical stress in humans. Anesthesiology 1981;55:120-6.  Back to cited text no. 14
Pierce JT, Kositratna G, Attiah MA, Kallan MJ, Koenigsberg R, Syre P, et al. Efficiency of spinal anesthesia versus general anesthesia for lumbar spinal surgery: A retrospective analysis of 544 patients. Local Reg Anesth 2017;10:91-8.  Back to cited text no. 15
Sadrolsadat SH, Mahdavi AR, Moharari RS, Khajavi MR, Khashayar P, Najafi A, et al. Aprospective randomized trial comparing the technique of spinal and general anesthesia for lumbar disk surgery: A study of 100 cases. Surg Neurol 2009;71:60-5.  Back to cited text no. 16
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Smith I, Kranke P, Murat I, Smith A, O'Sullivan G, Søreide E, et al. Perioperative fasting in adults and children: Guidelines from the European society of anaesthesiology. Eur J Anaesthesiol 2011;28:556-69.  Back to cited text no. 18
Allison SP, Tomlin PJ, Chamberlain MJ. Some effects of anaesthesia and surgery on carbohydrate and fat metabolism 1969. Br J Anaesth 1998;81:273-7.  Back to cited text no. 19
Møller IW, Hjortsø E, Krantz T, Wandall E, Kehlet H. The modifying effect of spinal anaesthesia on intra- and postoperative adrenocortical and hyperglycaemic response to surgery. Acta Anaesthesiol Scand 1984;28:266-9.  Back to cited text no. 20
Amiri F, Ghomeishi A, Aslani SM, Nesioonpour S, Adarvishi S. Comparison of surgical stress responses during spinal and general anesthesia in curettage surgery. Anesth Pain Med 2014;4:e20554.  Back to cited text no. 21
Milosavljevic SB, Pavlovic AP, Trpkovic SV, Ilić AN, Sekulic AD. Influence of spinal and general anesthesia on the metabolic, hormonal, and hemodynamic response in elective surgical patients. Med Sci Monit 2014;20:1833-40.  Back to cited text no. 22
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  [Full text]  
Kale A, Kale E, Erdemolu M, Akdeniz N, Canoruç N, Yayla M. The effect of general and spinal anaesthesia on maternal and newborn cortisol levels in elective cesarean deliveries. Perinat J 2006;14:141-6.  Back to cited text no. 25


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3]


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